Ultrasound catheter for providing a therapeutic effect to a vessel of a body

ABSTRACT

The invention relates to a catheter system. The system comprises a catheter body having a chamber containing a low acoustic impedance medium. The catheter body includes an elongated body with an external surface and an ultrasound transducer having an external side between a first end and a second end. The ultrasound transducer is positioned over the external surface of the elongated body such that the first end is adjacent to the chamber.

RELATIONSHIP TO CO-PENDING APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/383,292, filed Mar. 6, 2003, which is a continuation of U.S. patentapplication Ser. No. 09/375,162, filed Aug. 16, 1999, now U.S. Pat. No.6,582,392, which is a continuation-in-part of U.S. patent applicationSer. No. 09/129,980, filed Aug. 5, 1998, now U.S. Pat. No. 6,210,356, acontinuation-in-part of U.S. patent application Ser. No. 09/107,078,filed Jun. 29, 1998, now U.S. Pat. No. 6,723,063, and acontinuation-in-part of U.S. patent application Ser. No. 09/071,285,filed May 1, 1998, now U.S. Pat. No. 6,001,069, which claims priority toU.S. Provisional Application No. 60/045,268, filed May 1, 1997. Theentire disclosure of these priority applications is hereby incorporatedby reference herein in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a catheter, and more particularly, to acatheter having an ultrasound assembly.

2. Description of Related Art

Many medical treatments can be performed using catheters with anultrasound transducer. These ultrasound transducers deliver ultrasoundenergy to a target site within a patient. The ultrasound energy canprovide a therapeutic effect by itself or can enhance the effects ofother therapeutic media exposed to the ultrasound energy. Inefficientultrasound transducer arrangements can generate excessive heat during amedical treatment.

SUMMARY OF THE INVENTION

The invention relates to a catheter system. The system comprises acatheter body having a chamber containing a low acoustic impedancemedium. The catheter body includes an elongated body with an externalsurface and an ultrasound transducer having an external side between afirst end and a second end. The ultrasound transducer is positioned overthe external surface of the elongated body such that the first end ofthe ultrasound transducer is adjacent to the chamber.

Another embodiment of the system comprises a catheter body having anexternal surface. The catheter body includes an ultrasound transducerhaving a side between a first end and a second end. A first medium ispositioned adjacent to the first end of the ultrasound transducer and asecond medium is positioned adjacent to the external side of theultrasound transducer. The second medium is harder than the first mediumto encourage flexibility of the catheter body adjacent to the first endof the ultrasound transducer and efficient transmission of ultrasoundenergy from the external side of the ultrasound transducer.

The catheter system can also include a sheath for receiving thecatheter.

The invention also relates to a method for forming a catheter. Themethod includes positioning an ultrasound transducer over an externalsurface of an elongated body and positioning a collar over the externalsurface of the elongated body such that at least a portion of the collaris spaced apart from the ultrasound transducer. The method also includespositioning a transducer sheath over at least a portion of theultrasound transducer and over at least a portion of the collar to forma chamber between the ultrasound transducer and the collar.

Another embodiment of the method includes positioning a first spacerover an external surface of an elongated body and positioning a memberover at least a portion of the first spacer so as to form a chamberbetween the member and the external surface of the elongated body. Themethod also includes positioning an ultrasound transducer over themember.

Yet another embodiment of the method includes providing an ultrasoundtransducer having a side between a first end and a second end. Theultrasound transducer is positioned over an external surface of anelongated body. The method includes forming a first medium adjacent tothe first end of the ultrasound transducer and forming a second mediumadjacent to the side of the ultrasound transducer. The second medium isharder than the first medium to encourage flexibility of the catheterbody adjacent to the first end of the ultrasound transducer andefficient transmission of ultrasound energy from the external side ofthe ultrasound transducer.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A-1H illustrate a plurality of ultrasound assembles for use withcatheters according to the present invention.

FIG. 1A is a cross section of an ultrasound assembly having a chamberbetween an ultrasound transducer and an external surface of an elongatedbody.

FIG. 1B illustrates the relationship between spacers and the elongatedbody for the embodiment of the ultrasound assembly illustrated in FIG.1A.

FIG. 1C illustrates the relationship between the ultrasound transducerand the elongated body for the embodiment of the ultrasound assemblyillustrated in FIG. 1A.

FIG. 1D illustrates an ultrasound assembly having a chamber adjacent toan end of the ultrasound transducer and a chamber between the ultrasoundtransducer and the external surface of the elongated body.

FIG. 1E illustrates an ultrasound assembly having chambers adjacent toboth ends of the ultrasound transducer and a chamber between theultrasound transducer and the external surface of the elongated body

FIG. 1F illustrates an ultrasound assembly having a chamber adjacent toan end of the ultrasound transducer.

FIG. 1G illustrates an ultrasound assembly having chambers adjacent toboth ends of the ultrasound transducer.

FIG. 1H illustrates an ultrasound assembly without chambers.

FIGS. 2A-2D illustrate embodiments of ultrasound assemblies for use witha catheter according to the present invention. The ultrasound assembliesinclude a transducer sheath defining a reservoir at the end of theultrasound assembly. The reservoir contains a binding medium.

FIGS. 3A-3D illustrate embodiments of ultrasound assemblies for use witha catheter according to the present invention. The ultrasound assembliesinclude an assembly sheath positioned over an ultrasound transducer. Avolume between the ultrasound transducer and the assembly sheathcontains a binding medium.

FIGS. 4A-4F illustrate ultrasound assemblies having a spacer forcreating a chamber between a side of an ultrasound transducer and anexternal surface of an elongated body. The ultrasound assemblies alsoinclude a collar for creating a chamber adjacent to the ends of theultrasound transducer.

FIG. 4A illustrates the collar abutting the spacer.

FIG. 4B illustrates the collar in a spaced apart relationship to thespacer.

FIGS. 4C and 4D illustrate the collar positioned over the spacer.

FIGS. 4E and 4F illustrate the collar integral with the spacer.

FIG. 5A illustrates a catheter incorporating an ultrasound assembly.

FIG. 5B illustrates catheter having a binding medium adjacent to theends of the ultrasound transducer.

FIG. 5C illustrates a catheter having a binding medium adjacent to theexternal side of the ultrasound transducer.

FIG. 5D illustrates a catheter having a binding medium adjacent to theends of the ultrasound transducer and another binding medium adjacent tothe external side of the ultrasound transducer.

FIG. 5E illustrates a catheter having a binding medium adjacent to theends of the ultrasound transducer and a second binding medium adjacentto the external surface of the catheter ultrasound transducer and athird binding medium adjacent to the ultrasound transducer.

FIG. 5F illustrates a catheter having a binding medium adjacent to theends of the ultrasound transducer, a second binding medium adjacent tothe external side of the ultrasound transducer and a third bindingmedium positioned in reservoirs at the ends of the ultrasound assembly.

FIGS. 6A-6C illustrate embodiments of a catheter having a plurality ofultrasound assemblies according to the present invention.

FIG. 6A illustrates a catheter having ultrasound assemblies spaced apartfrom a catheter sheath.

FIG. 6B illustrates a catheter having ultrasound assemblies in contactwith a catheter sheath.

FIG. 6C illustrates a catheter having ultrasound assemblies which sharea member.

FIGS. 7A-7E illustrate a method for forming ultrasound assembliesaccording to the present invention.

FIGS. 8A-8D illustrate a method for forming an ultrasound assembly whena collar for forming a chamber adjacent to the ultrasound transducer isintegral with a spacer for forming a chamber between the ultrasoundtransducer and an external surface of an elongated body.

FIG. 9A illustrates a method for forming an ultrasound assembly having atransducer sheath extending beyond the ultrasound transducer and beyonda collar so as to form reservoirs adjacent to the ends of the ultrasoundtransducer.

FIG. 9B illustrates delivery of a binding medium into a reservoir at anend of the ultrasound assembly.

FIGS. 10A-10D illustrate a method for forming a catheter according tothe present invention.

FIG. 10A illustrates a catheter sheath positioned over an extensionregion, an assembly region and a terminal region of a catheter body.

FIG. 10B illustrates a binding medium delivered adjacent to an end ofthe ultrasound transducer.

FIG. 10C illustrates a binding medium delivered adjacent to an externalside of the ultrasound transducer.

FIG. 10D illustrates a first binding medium delivered adjacent to anexternal side of the ultrasound transducer and a second binding mediumdelivered adjacent to an end of the ultrasound transducer.

FIG. 11 illustrates the proximal portion of a catheter according to thepresent invention.

FIGS. 12A-12D illustrate a sheath for use with a catheter according tothe present invention.

FIG. 12A is a sideview of the sheath.

FIG. 12B illustrates a catheter according to the present inventionpositioned within the sheath.

FIG. 12C is a sideview of a sheath having a drug delivery lumen whichspirals around a sheath distal end.

FIG. 12D is a cross section of a sheath having a drug delivery lumenwhich spirals around a sheath distal end.

FIGS. 13A-13G illustrate a method for using a catheter according to thepresent invention in conjunction with a sheath.

FIG. 14A is a sideview of a catheter with segmented ultrasound elements.

FIG. 14B illustrates the catheter of FIG. 1A positioned within a vesselof a body.

FIG. 15A illustrates ultrasound elements connected in series.

FIG. 15B illustrates ultrasound elements connected in-parallel.

FIG. 15C illustrates ultrasound elements or temperature sensorsconnected through a common wire.

FIG. 16A is a cross section of a catheter with a lumen coupled with drugdelivery ports which are each correlated with an ultrasound element.

FIG. 16B is a cross section of a catheter with a first lumen fordelivering drug through first drug delivery ports and a second lumen fordelivering drug through second drug delivery ports.

FIG. 17A is a sideview of a catheter including ribs between ultrasoundelements.

FIG. 17B is a cut-away view a catheter including webbing or mesh betweenthe ultrasound elements.

FIG. 17C is a cross section of the catheter of FIG. 4B.

FIG. 18 is a schematic of a feedback control system for a catheterincluding a plurality of ultrasound elements.

DESCRIPTION

The invention relates to a catheter having a chamber containing a lowacoustic impedance medium. The catheter can also include an elongatedbody with an external surface. An ultrasound transducer having anexternal side between a first end and a second end can be positionedover the external surface of the elongated body such that the first sideof the ultrasound transducer is adjacent to the chamber.

The low acoustic impedance material within the chamber reduces theportion of ultrasound energy which is transmitted through the chamber.This reduction causes an increased portion of ultrasound energy to bedelivered from the second end of the ultrasound transducer and/or fromthe external side of the ultrasound transducer. As a result, theultrasound energy produced from these sections of the ultrasoundtransducer is delivered with a greater efficiency.

The ultrasound transducer can be positioned distally relative to thechamber in order to increase the efficiency of the ultrasound energytransmitted in the distal direction. Alternatively, the ultrasoundtransducer can be positioned proximally relative to the chamber in orderto increase the efficiency of the ultrasound energy transmitted in theproximal direction.

Another embodiment of the catheter includes a chamber between theelongated body and an internal side of the ultrasound transducer. Thechamber can include a low acoustic impedance medium to reduce theportion of ultrasound energy transmitted into the elongated body. As aresult, the ultrasound energy produced from the ends and the externalside of the ultrasound transducer is delivered with a greater efficiencythan could be achieved without the chamber.

A catheter according to the present invention can include variouscombinations of the above chambers. Each of the chambers can beindependent of one another or they can be in communication with oneanother. The chambers can contain a low acoustic impedance medium. Forinstance, a catheter can include a first chamber adjacent to the firstend of the ultrasound transducer, a second chamber adjacent to thesecond end of the ultrasound transducer and a third chamber between theinternal side of the ultrasound transducer and the elongated body. As aresult, the ultrasound energy produced from the external surface of thecatheter is delivered at an increased efficiency. Such a catheterefficiently delivers ultrasound energy from the side of the catheter.

As another example, a catheter can include the first chamber adjacent tothe first end of the ultrasound transducer and the third chamber betweenthe internal side of the ultrasound transducer and the elongated body.Further, the ultrasound transducer can be positioned distally relativeto the first chamber. The chambers can contain a low acoustic impedancemedium. As a result, the ultrasound energy produced from the second endand the external surface of the catheter is delivered at an increasedefficiency. Such a catheter efficiently delivers ultrasound energy bothdistally and from the side of the catheter.

A catheter according to the present invention can also include aplurality of ultrasound transducers. Each ultrasound transducer can beassociated with one or more chambers. As a result, each ultrasoundtransducer can have an increased efficiency.

An embodiment of a catheter having a plurality of ultrasound transducersincludes ultrasound transducers with matched resonant frequencies. Forinstance, the catheter can include ultrasound transducers selected suchthat any one has a resonant frequency within about 1% of the resonantfrequency of any other ultrasound transducer in the plurality ofultrasound transducers. The matching of the ultrasound transducersallows the ultrasound transducers to be concurrently driven at a singlefrequency while reducing the inefficiencies associated with drivingultrasound transducers at a frequency which is significantly differentthan their resonant frequency.

Another embodiment of the catheter includes a first binding mediumadjacent to the first end of the ultrasound transducer and a secondbinding medium adjacent to the external side of the ultrasoundtransducer. The first and second media are selected to provide thecatheter with flexibility and a high level of ultrasound transmissionefficiency. Since a softer media is typically more flexible and hardermedia typically transit ultrasound energy more efficiently, the secondmedium is preferably harder than the first medium. The advantages of thefirst and second media are emphasized in multiple ultrasound transducercatheters which tend to lose flexibility with the increased number ofultrasound transducers.

Catheters according to the present invention can also include anautotransformer in the proximal portion of the catheter. Theautotransformer can serve to adjust the characteristic impedance of thecatheter to match the impedance of components used to drive the one ormore ultrasound transducers included on the catheter. The matchedimpedance serves to increase the efficiency of the catheter system.

Catheters according to the present invention can also include a catheteridentification electronics. The catheter identification electronicsindicate to a catheter control system the frequency that ultrasoundtransducers should be driven.

FIGS. 1A-1C illustrate an embodiment of an ultrasound assembly 10according to the present invention for use with a catheter according tothe present invention. FIG. 1A is a longitudinal cross sectional view ofthe ultrasound assembly 10. FIG. 1B is a lateral cross section of theultrasound assembly 10 taken at the point labeled A in FIG. 1A. FIG. 1Cis a lateral cross section of the ultrasound assembly 10 taken at thepoint labeled B in FIG. 1A.

The ultrasound assembly 10 includes an elongated body 12 with anexternal surface 14. A plurality of spacers 16 are positioned over theexternal surface 14 of an elongated body 12 and a member 18 ispositioned over at least a portion of the spacers 16. The ultrasoundassembly 10 also includes an ultrasound transducer 20 with an externalside 22 and an internal side 24 between a first end 26 and a second end28. The ultrasound transducer 20 is positioned over the member 18 andcan surround the member 18. Suitable materials for the member 18include, but are not limited to, polyimide, polyester and nylon. Asuitable ultrasound transducer 20 includes, but is not limited to,PZT-4D, PZT-4, PZT-8 and various piezoceramics.

The internal side 24 of the ultrasound transducer 20, the spacers 16 andthe member 18 each define a portion of a chamber 30 between the internalside 24 of the ultrasound transducer 20 and the external surface 14 ofthe elongated body 12. The chamber 30 preferably has a height from0.25-10 μm, more preferably from 0.50-5 μm and most preferably from0.0-1.5 μm.

The member 18 can extend beyond the first end 26 and/or the second end28 of the ultrasound transducer 20. Additionally, the spacers 16 can bepositioned beyond the ends of the ultrasound transducer 20. As a result,the chamber 30 can extend along the longitudinal length of theultrasound transducer 20 to increase the portion of the ultrasoundtransducer 20 which is adjacent to the chamber 30.

The chamber 30 can contain a low acoustic impedance medium. Suitable lowacoustic impedance media include, but are not limited to, fluids such ashelium, argon, air and nitrogen and/or solids such as silicone andrubber. The chamber 30 can also be evacuated. Suitable pressures for anevacuated chamber 30 include, but are not limited to, negative pressuresto −760 mm Hg.

As illustrated in FIG. 1D, the internal side 24 of the ultrasoundtransducer 20 can also be positioned adjacent to a chamber 30. Theultrasound assembly 10 includes a collar 32 over external surface 14 ofthe elongated body 12. The collar 32 can surround the elongated body 12.The collar 32 has a spaced apart relationship to the ultrasoundtransducer 20.

A transducer sheath 34 is positioned over at least a portion of theultrasound transducer 20 and the collar 32 to form a chamber 30 adjacentto a side of the ultrasound transducer 20. An inner side of the collar32, the ultrasound transducer 20 and the transducer sheath 34 eachpartially define the chamber 30. The chamber 30 preferably has a width,W, from 12-2500 μm, more preferably from 25-250 μm and most preferablyfrom 25-125 μm. The chamber 30 can contain a low acoustic impedancemedium. Suitable materials for the transducer sheath 34 include, but arenot limited to air, N₂, O₂, and vacuum. The transducer sheath 34preferably has a thickness from 10-100 μm and more preferably from 25-50μm.

The ultrasound assembly 10 can also include a chamber 30 adjacent to thesecond end 28 of the ultrasound transducer 20 as illustrated in FIG. 1E.A second collar 36 is positioned over the elongated body 12 and cansurround the external surface 14 of the elongated body 12. The secondcollar 36 has a spaced apart relationship from the ultrasound transducer20 so as to provide a second chamber 30 adjacent to the ultrasoundtransducer 20. An inner side of the second collar 36, the ultrasoundtransducer 20 and the transducer sheath 34 each partially define thechamber 30. The chamber 30 preferably has a width, W, from 12-2500 μm,more preferably from 25-250 μm and most preferably from 25-125 μm. Thechamber 30 adjacent to the second end 28 of the ultrasound transducer 20can also contain a low acoustic impedance medium.

Each of the chambers can be isolated from one another. However, when theultrasound assembly 10 includes a chamber 30 between the ultrasoundtransducer 20 and the elongated body 12, one or more of the spacers 16can be formed of a porous material to provide communication between thechambers 30. This communication can permit the pressures in each of thechambers 30 to reach an equilibrium. Alternatively, one or more of thespacers 16 can include channels, lumens 38 and/or a ridged externalsurface to permit the communication between chambers 30.

An embodiment of the ultrasound assembly 10 does not include a chamber30 between the elongated body 12 and the internal side 24 of theultrasound transducer 20 as illustrated in FIG. 1F. The ultrasoundtransducer 20 is positioned adjacent to the external surface 14 of theelongated body 12 such that a chamber 30 is not formed between theelongated body 12 and the ultrasound transducer 20. The ultrasoundassembly 10 includes a collar 32 around the elongated body 12 in aspaced apart relationship from the ultrasound transducer 20 so as toform a chamber 30 adjacent to the first side of the ultrasoundtransducer 20.

The ultrasound assembly 10 of FIG. 1F can also include a second chamber30 adjacent to the second end 28 of the ultrasound transducer 20 asillustrated in FIG. 1G. The ultrasound assembly 10 includes a secondcollar 36 over the elongated body 12 in a spaced apart relationship fromthe ultrasound transducer 20. Accordingly a second chamber 30 is formedadjacent to the second side of the ultrasound transducer 20. Asillustrated in FIG. 1H, an embodiment of the ultrasound assembly 10 doesnot include any chambers 30.

A utility lumen 38 extends through the elongated body 12. The utilitylumen 38 can be sized to receive a guidewire, to deliver therapeuticmedia including drugs, medication, microbubbles and other compoundswhich provide a therapeutic effect. Although, the elongated body 12 isillustrated as having a single utility lumen 38, the elongated body 12can include a plurality of lumens 38 or can be solid.

Each of the ultrasound assemblies 10 illustrated in FIGS. 1A-1H can havea transducer sheath 34 which extends past the first collar 32, thesecond collar 36 and/or past the ultrasound transducer 20. FIGS. 2A-2Dillustrate such a transducer sheath 34 with a selection of theultrasound assemblies 10 illustrated in FIGS. 1A-1H. The extension ofthe transducer sheath 34 past the collar 32 and/or past the ultrasoundtransducer 20 provides a reservoir 40 at the ends of the ultrasoundassembly 10. The reservoir 40 can optionally contain a binding medium 42such as an epoxy or adhesive. The binding medium 42 can serve to keepthe ultrasound transducer 20 intact during the handling of theultrasound assembly 10. Although FIGS. 2A-2D illustrate the transducersheath 34 extending past the first collar 32, the second collar 36and/or the ultrasound transducer 20 at both ends of the ultrasoundassembly 10, the transducer sheath 34 can extending past a collar 32and/or ultrasound transducer 20 at only one end of the ultrasoundassembly 10.

Each ultrasound assembly 10 discussed and/or suggested above can includean assembly 10 sheath. FIGS. 3A-3D illustrate a selection of the aboveultrasound assemblies 10 including an assembly sheath 44 positioned overthe ultrasound transducer 20. Suitable materials for the assembly sheath44 include, but are not limited to polyimide, PTFE, and polyurethane.The assembly sheath 44 preferably has a thickness from 12-75 μm and morepreferably from 25-50 μm.

A volume between the assembly sheath 44 and the ultrasound transducer 20can contain a binding medium 42 as illustrated in FIG. 3A. Further, whenthe ultrasound assembly 10 includes a transducer sheath 34, the volumebetween the ultrasound assembly 10 sheath and the transducer sheath 34can contain the binding medium 42 as illustrated in FIGS. 3B-3D. Thebinding medium 42 can be a binding medium 42 which serves to keep theultrasound transducer 20 intact during the handling of the ultrasoundassembly 10.

Each of the ultrasound assemblies 10 illustrated above show theelongated body 12 extending outward from the ultrasound assembly 10.However, the elongated body 12 can be trimmed to provide an elongatedbody 12 which is flush with one or more sides of the elongated body 12.Additionally, a sensor such as a temperature sensor can be positioned inthe binding medium 42 associated with any of the above ultrasoundassemblies 10.

FIGS. 4A-4F illustrate various arrangements between the collars 32 andspacers 16 for use with the ultrasound assemblies 10 discussed above.FIG. 4A illustrates the collar 32 abutting the spacers 16. The collar 32can be spaced apart from the spacers 16 as illustrated in FIG. 4B. Inanother embodiment, the collar 32 is sized to be positioned around thespacer 16 as illustrated in FIG. 4C. In yet another embodiment, thecollar 32 is sized to be positioned around the member 18 as illustratedin FIG. 4D.

The collar 32 can be integral with the spacers 16 as illustrated in FIG.4E. The spacer 16 has an L-shaped profile with a spacer region 46positioned adjacent to the member 18 and a collar region 48 positionedadjacent to the transducer sheath 34. Accordingly, the raised edgeserves to define a side of the chamber 30. When the collar 32 isintegral with the spacer, the spacer 16 can include a seat 50 sized toreceive an edge of the member 18 as illustrated in FIG. 4F.

FIGS. 5A and 5B illustrate a catheter according to the presentinvention. The catheter can include any of the ultrasound assemblies 10discussed or suggested above. As a result, the catheter is illustratedwith a generalized representation of an ultrasound assembly 10.Specifically, an ultrasound assembly 10 is illustrated as an ultrasoundtransducer 20 over an elongated body 12. A box 51 over the ultrasoundtransducer 20 represents the remaining portions of each ultrasoundassembly 10. For instance, the box 51 can represent the collars 32,spacers, members, chambers, binding media, etc. associated with anultrasound assembly 10.

The catheter includes a catheter body 52 having an external surface 53,a distal portion 54 and a proximal portion 56. The catheter body 52 caninclude an extension region 58, an assembly region 60 and a terminalregion 62. Lumens 38 within the extension region 58, assembly region 60and terminal region 62 are aligned with one another to provide one ormore lumens 38 extending through the entire catheter. These lumens 38can be sized to receive a guidewire or for the delivery of a therapeuticagent such as a drug.

The extension region 58 includes an extension body 64 having one or morelumens 38. The one or more lumens 38 included in the extension body 64have cross sectional dimensions approximating the cross sectiondimensions of the one or more utility lumens 38 of the elongated body12. The extension body 64 can be used to add length to the catheter.Specifically, the extension body 64 can provide additional length beyondthe length provided by the assembly region 60. Accordingly, theextension body 64 can be short or can be eliminated from the catheterbody 52. Suitable materials for the extension body 64 include, but arenot limited to, polyimide, silicone, and polyurethane.

The terminal region 62 is positioned at the distal tip of the catheter.The terminal region 62 includes a terminal body 66. The terminal body 66can be solid or include one or more lumens 38 with cross sectionaldimensions approximating the cross section dimensions of the one or moreutility lumens 38 of the elongated body 12. Suitable materials for theterminal region 62 include, but are not limited to, polyimide, silicone,and polyurethane. The assembly region 60 is the region of the catheterbody 52 including any of the ultrasound assemblies 10 discussed and/orsuggested above.

A catheter sheath 68 is positioned over the extension region 58, theassembly region 60 and the terminal region 62 so as to define a portionof the external surface 53 of the catheter body 52. The catheter sheath68 can serve to immobilize the extension region 58, the assembly region60 and the terminal region 62 relative to one another. The cathetersheath 68 is optional and can be removed from the catheter body 52.

The volume between the ultrasound assembly 10 and the extension body 64can contain a binding medium 42. Such binding media can serve to couplethe extension region 58, the assembly region 60 and the terminal region62 together. Suitable materials for the catheter sheath 68 include, butare not limited to polyethelyne, polyurethane, and polyimide. Thethickness of the catheter sheath 68 material is preferably 0.001″ to0.020″, more preferably 0.004″ to 0.010″ and most preferably 0.006″ to0.008″.

As illustrated in FIG. 5B, a first binding medium 42A can be positionedadjacent to the ends of the ultrasound transducer 20. Specifically, avolume between the extension body 64 and the ultrasound transducer 20can contain the first binding medium 42A. Further, the volume betweenthe terminal body 66 and the ultrasound transducer 20 can contain thefirst binding medium 42A.

The first binding medium 42A can also be positioned adjacent to theexternal side 22 of the ultrasound transducer 20 as illustrated in FIG.5C. Specifically, the first binding medium 42A can be contained in avolume between the external side 22 of the ultrasound transducer 20 andthe externals surface of the catheter body 52.

As illustrated in FIG. 5D, a catheter can include a first binding medium42A and a second binding medium 42B. The first binding medium 42A isadjacent to the ends of the ultrasound transducer 20 and the secondbinding medium 42B is adjacent to the external side 22 of the ultrasoundtransducer 20. Specifically, the second binding medium 42B can becontained in a volume between the external side 22 of the ultrasoundtransducer 20 and the external surface 53 of the catheter body 52. Aportion of the second binding medium 42B is also illustrated as beingadjacent to the ends of the ultrasound assembly 10 although the secondbinding medium 42B can be restricted to the volume adjacent to theexternal side 22 of the ultrasound transducer 20.

The first binding medium 42A and the second binding medium 42B can bethe same or different. When the second binding medium 42B is differentthan the first binding medium 42A, the second binding medium 42B ispreferably harder than the first binding medium 42A. A harder bindingmedium 42 typically transmits ultrasound energy more efficiently than asofter binding medium 42. As a result, the hardness of the secondbinding medium 42B can preserve the ultrasound transmitting efficiencyof the catheter. Additionally, the softness of the first binding medium42A provides the catheter with additional flexibility. As a result, thechoices of the first and second binding media effect both theflexibility and the ultrasound transmission efficiency of the catheter.

The second binding medium 42B is preferably at least 2 times harder thanthe first binding medium 42A and more preferably from about 3 to about 5times harder than the first binding medium 42A. The first binding medium42A preferably has a hardness of at least about 10 Shore D, morepreferably from about 15 to about 80 Shore D and most preferably fromabout 20 to about 40 Shore D. The second binding medium 42B preferablyhas a hardness of at least about 60 Shore D, more preferably from about65 to about 120 Shore D and most preferably from about 80 to about 100Shore D.

As described above, any of the ultrasound assemblies 10 described and/orsuggested above can be included in a catheter according to the presentinvention. FIG. 5E illustrates a particular example of a catheterincluding an assembly sheath 44 over the ultrasound transducer 20.Specifically, FIG. 5B illustrates the catheter including the ultrasoundassembly 10 of FIG. 2B. The ultrasound assembly 10 includes a chamber 30adjacent to a first end 26 of the ultrasound transducer 20. The chamber30 is positioned proximally relative to the ultrasound transducer 20.The ultrasound assembly 10 includes another chamber 30 between theultrasound transducer 20 and the external surface 14 of the elongatedbody 12. Each chamber 30 contains a low acoustic impedance medium. As aresult, this embodiment of the catheter efficiently transmits ultrasoundenergy in the distal direction.

The catheter of FIG. 5E includes a first binding medium 42A, a secondbinding medium 42B and a third binding medium 42C. The first bindingmedium 42A is adjacent to the ends of the ultrasound transducer 20 andthe second binding medium 42B is contained in a volume between theassembly sheath 44 and the external surface 53 of the catheter body 52.The third binding medium 42C is adjacent to the external side 22 of theultrasound transducer 20. Specifically, a volume between the ultrasoundtransducer 20 and the assembly sheath 44 includes the third bindingmedium 42C.

Two or more of the first, second and third binding media can be the sameor they can all be different. In a preferred embodiment, the first andsecond binding media are the same while the third binding medium 42Ctransmits is harder than the first and second binding media.Accordingly, when the first and second binding media are the same, thethird binding media is preferably harder than the first binding medium42A. Preferably, the first binding medium 42A is also more flexible thanthe third binding medium 42C. Further, the third binding medium 42C ispreferably at least 2 times harder than the first binding medium 42A andmore preferably from about 3 to about 5 times harder than the firstbinding medium 42A. Additionally, the first binding medium 42Cpreferably has a hardness of at least about 10 Shore D, more preferablyfrom about 15 to about 80 Shore D and most preferably from about 20 toabout 40 Shore D. The third binding medium 42B preferably has a hardnessof at least about 60 Shore D, more preferably from about 65 to about 120Shore D and most preferably from about 80 to about 100 Shore D. Inanother preferred embodiment, the second and third binding media areeach harder than the first binding medium 42A. In another preferredembodiment, the second and third binding media are the same and areharder than the first binding medium 42A.

FIG. 5F illustrates a particular example of a catheter having atransducer sheath 34 extending beyond the collar 32 and the ultrasoundtransducer 20 to form reservoirs 40 at the end of the ultrasoundassembly 10. The catheter includes a first binding medium 42A, a secondbinding medium 42B and a third binding medium 42C. The first bindingmedium 42A is adjacent to the ends of the ultrasound transducer 20 andthe second binding medium 42B is adjacent to the external side 22 of theultrasound transducer 20. Reservoirs 40 formed adjacent to the ends ofthe ultrasound transducer 20 contain the third binding medium 42C.

Two or more of the first, second and third binding media can be the sameor they can all be different. The second binding medium 42B preferablytransmits ultrasound energy more efficiently than the first bindingmedium 42A. Further, the first binding medium 42A is preferably moreflexible than the second binding medium 42B. The first and secondbinding media preferably have the hardness relationships and levelsdescribed with respect to the first and second binding media of FIG. 5D.In a preferred embodiment, the first and third binding media are thesame.

The catheter can include two or more ultrasound assemblies 10 asillustrated in FIGS. 6A and 6B. FIG. 6A illustrates the ultrasoundassembly 10 in contact with the catheter sheath 68 while FIG. 6Billustrates the ultrasound assemblies 10 spaced apart from the cathetersheath 68. The ultrasound assemblies 10 can share the same elongatedbody 12 and/or different ultrasound assemblies 10 can include differentelongated bodies 12. When the ultrasound assemblies 10 are formed withdifferent elongated bodies 12, the different elongated bodies 12 can bealigned with one another during assembly of the catheter.

Two or more ultrasound assemblies 10 can share a member 18 asillustrated in FIG. 6C. Each of the ultrasound assemblies 10 ispositioned over the same member 18. As a result, the member 18 partiallydefines a chamber 30 between each of the ultrasound transducers 20 andthe elongated body 12. When different ultrasound transducers 20 share amember 18, spacers 16 can be optionally positioned between theultrasound assemblies 10. As a result, a single member 18 can bepositioned over at least a portion of three or more spacers 16.

As illustrated in FIGS. 6A and 6B, when the catheter includes aplurality of ultrasound transducers 20, a first binding medium 42A canbe positioned adjacent to the ends of the ultrasound transducers 20.Specifically, the first binding medium 42A can be contained in a volumebetween an ultrasound transducer 20 and an extension body 64, a volumebetween adjacent ultrasound transducer 20, and/or a volume between anultrasound transducer 20 and a terminal body 66.

As illustrated in FIG. 6C, a catheter including a plurality ofultrasound assemblies 10 can also include a second binding medium 42Badjacent to the external side 22 of the ultrasound transducers 20.Specifically, the second binding medium 42B can be contained in a volumebetween the external side 22 of the ultrasound transducer 20 and theexternal surface 53 of the catheter body 52. As described with respectto FIG. 5D, the first and second binding media can be the same ordifferent and the second binding medium 42B is preferably harder thanthe first binding medium 42A. As described with respect to FIGS. 5E-5F,the inclusion of specific ultrasound assembly 10 embodiments can resultin the catheter including additional binding media. When the catheterincludes an additional binding media adjacent to the external side 22 ofthe ultrasound transducers 20 (i.e. FIG. 5E), that binding media ispreferably at least as hard as the first and second binding media.

FIGS. 7A-7E illustrate a method for fabricating ultrasound assemblies 10according to the present invention. In FIG. 7A, spacers 16 arepositioned over an elongated body 12. The spacers 16 can optionally beadhesively attached to the elongated body 12 with compounds such asepoxy. FIG. 7B illustrates a member 18 positioned over the spacers 16.The positioning of the member 18 forms a chamber 30 between the member18 and the elongated body 12. The member 18 can optionally be adhesivelyattached to the spacers 16 with compounds such as epoxy.

In FIG. 7C an ultrasound transducer 20 is positioned over the member 18to form the ultrasound assembly 10 of FIG. 1A. The ultrasound transducer20 can optionally be adhesively attached to the member 18 with compoundssuch as epoxy. A collar 32 is also positioned over the elongated body 12and can be attached to the elongated body 12 with compounds such asepoxy. FIG. 7D illustrates a transducer sheath 34 positioned over thecollar 32 to form the ultrasound assembly 10 of FIG. 2B. The transducersheath 34 forms a chamber 30 adjacent to the ultrasound transducer 20.

In FIG. 7E an assembly sheath 44 is positioned over the transducersheath 34 of the ultrasound assembly 10 illustrated in FIG. 7D. Abinding medium 42 precursor is delivered adjacent to the external side22 of the ultrasound transducer 20. Specifically, the binding medium 42precursor is delivered into a volume between the transducer sheath 34and the assembly sheath 44. The binding medium 42 can be delivered intothe volume using an injection device such as a hypodermic needle 70. Thebinding medium 42 can solidify to provide the ultrasound assembly 10 ofFIG. 3B. Suitable mechanisms for solidification include, but are notlimited to, setting, cooling and curing.

FIGS. 8A-8D illustrate method for forming ultrasound assemblies 10 whenthe collar 32 is integral with the spacers 16. FIG. 8A illustrates aspacer 16 positioned over an elongated body 12. In FIG. 8B a member 18is positioned over the spacer 16 and an ultrasound transducer 20 ispositioned over the member 18. In FIG. 8C a second spacer 16 ispositioned over the elongated body 12 and moved toward the originalspacer 16 until a portion of the spacer 16 is positioned between themember 18 and the elongated body 12. As a result, a chamber 30 is formedbetween the member 18 and the elongated body 12. In FIG. 8D a transducersheath 34 is positioned over the spacers 16 and the ultrasoundtransducer 20 to form the ultrasound assembly 10 of FIG. 3C havingcollars 32 which are integral with the spacers 16.

FIGS. 9A-9B illustrate an adaptation of the method illustrated in FIGS.7A-7E to form an ultrasound assembly 10 having a transducer sheath 34which extends past a first collar 32, a second collar 36 and/or past theultrasound transducer 20 as discussed with respect to FIGS. 2A-2D. FIG.9A illustrates a transducer sheath 34 positioned over the collar 32 andultrasound transducer 20 of FIG. 7C. The ultrasound transducer 20extends past the collar 32 and the ultrasound transducer 20 to formreservoirs 40 adjacent to the ends of the ultrasound transducer 20. FIG.9B illustrates a binding medium 42 precursor being delivered into thereservoirs 40 to provide the ultrasound assembly 10 illustrated in FIG.2B.

The methods described in FIGS. 7A-9B can be used to provide an elongatedbody 12 having a plurality of ultrasound assemblies 10. Each ultrasoundassembly 10 can be concurrently formed on the elongated body 12 or theycan be sequentially formed on the elongated body 12. Alternatively, aportion of each ultrasound assembly 10 can be formed concurrently whilethe remaining portions of the ultrasound assemblies 10 are formedsequentially. For instance, in FIG. 6C, the chamber 30 between eachultrasound transducer 20 and the external surface 14 of the elongatedbody 12 can be formed concurrently while the remaining portions of theultrasound assemblies 10 are formed sequentially.

FIGS. 10A-10D illustrate methods for forming a catheter according to thepresent invention. FIG. 10A illustrates a catheter sheath 68 positionedover an extension body 64 as illustrated by the arrow labeled A. Theultrasound assembly 10 is then positioned within the catheter sheath 68as illustrated by the arrow labeled B. A terminal body 66 is thenpositioned within the catheter sheath 68 as indicated by the arrowlabeled C.

As illustrated in FIG. 10B, a binding medium 42 precursor is deliveredadjacent to an end of the ultrasound transducer 20. Specifically, thebinding medium 42 precursor is delivered into a volume between theultrasound assembly 10 and the terminal body 66. FIG. 10B illustratesthe binding medium 42 precursor delivered adjacent to an end of theultrasound assembly 10 using an injection instrument such as ahypodermic needle 70. The binding medium 42 precursor can besequentially delivered adjacent to one end of the ultrasound transducer20 and then adjacent to the opposing end of the ultrasound transducer20. The binding medium 42 precursor preferably solidifies to form abinding media adjacent to the ends of the ultrasound transducer 20.

As illustrated in FIG. 10C, a binding medium 42 precursor can also bedelivered into a volume between the external side 22 of the ultrasoundtransducer 20 and the external surface 53 of the catheter body 52. Asillustrated, the quantity of binding medium 42 precursor delivered canbe enough to fill the volume adjacent to the external side 22 of theultrasound transducer 20. The binding medium 42 precursor preferablysolidifies to form a binding medium 42 adjacent to the external side 22of the ultrasound transducer 20. Alternatively, sufficient bindingmedium 42 precursor can be delivered to fill the volume adjacent to theends of the ultrasound transducer 20.

When the quantity of binding medium 42 precursor delivered fills thevolume adjacent to the external side 22 of the ultrasound transducer 20,a second binding medium 42B precursor can be delivered into the volumesadjacent to the ends of the ultrasound transducer 20 as illustrated inFIG. 10D. The second binding medium 42B precursor preferably solidifiesto form a second binding medium 42B adjacent to the ends of theultrasound transducer 20.

Once the binding media delivered above have solidified, the cathetersheath 68 can be removed from the catheter body 52. Additionally, once achamber 30 is formed, a fluid low acoustic impedance medium can bedelivered into the chamber 30. A low acoustic impedance mediumpreferably has an acoustic impedance less than about 1.7 Megarayls, morepreferably of about 0-0.7 Megarayls and most preferably from 0-0.4Megarayls. As described above, suitable low acoustic impedance mediainclude, but are not limited to, helium, argon, air and nitrogen. Thesemedia can be delivered into the chamber 30 during or after the mediasolidification process using an injection device such as a hypodermicneedle 70. Similar techniques can be used to draw a vacuum within thechamber 30. Solid low acoustic impedance media such as silicones andrubbers can be positioned within the chamber 30 during the formation ofthe ultrasound assembly 10.

The methods for forming a catheter described with respect to FIGS.10A-10D can be used to form a catheter having multiple ultrasoundassemblies 10. For instance, the elongated body 12 illustrated in FIG.10A can be replaced with an elongated body 12 having a plurality ofultrasound assemblies 10. Alternatively, several independent elongatedbodies 12 having ultrasound assemblies 10 can be sequentially positionedwithin the catheter sheath 68. The one or more lumens 38 in adjacentelongated bodies 12 are aligned before binding medium 42 precursor isdelivered into the volume defined by the catheter sheath 68. Additionalcatheters having a plurality of ultrasound transducers are described inU.S. patent application Ser. No. 09/071,285, filed May 1, 1998 andentitled Ultrasound Catheter for Providing a Therapeutic Effect to aVessel of a Body which is incorporated herein in its entirety.

When the ultrasound assembly 10 or catheter includes multiple ultrasoundtransducers 20, the methods for forming the ultrasound assembly 10 orcatheter can include matching the resonant frequencies of the ultrasoundtransducers 20. For instance, the ultrasound transducers 20 can beselected such that any member of the plurality of ultrasound transducers20 has a resonant frequency within about 10% of the resonant frequencyof any other ultrasound transducer 20. More preferably, the ultrasoundtransducers 20 are selected such that any one has a resonant frequencywithin about 3%, even more preferably within about 1% and mostpreferably within about 0.5% of any other ultrasound transducer 20 inthe plurality of ultrasound transducers 20. The selected ultrasoundtransducers 20 are then used to form an ultrasound assembly 10 orcatheter.

The matching of the ultrasound transducers 20 allows the ultrasoundtransducers to be concurrently driven at a single frequency whilereducing the inefficiencies associated with driving ultrasoundtransducers 20 at a frequency which is significantly different thantheir resonant frequency. Since the ultrasound transducers 20 can bedriven at a single frequency, the matching the resonant frequencies ofthe ultrasound transducers 20 is preferred when the plurality ofultrasound transducers 20 are connected in parallel or in series.

The electrical connections for driving the one or more ultrasoundtransducers 20 can be done at various stages during the assembly of thecatheter and/or ultrasound assembly 10. For instance, electrical wirescan be coupled with the ultrasound transducers 20 before the ultrasoundtransducers 20 are positioned over the elongated body. Additionally, theelectrical wires can be coupled with the ultrasound transducers 20 afterthe ultrasound transducers 20 are in position over the elongated body.Further, electrical connections can be made alternating with positioningthe ultrasound transducers 20 over the elongated body.

Alternatively, one or more electrical wires can be positioned along theelongated body before the ultrasound transducers 20 are positioned overthe elongated body. One or more ultrasound transducers 20 can then beslid over the elongated body such that the one or more electrical wirescontact the inner side of the ultrasound transducers 20. The contactbetween the ultrasound transducers 20 and the electrical wire can serveas the electrical connection to the one or more ultrasound transducers20. When a catheter or ultrasound assembly 10 includes more than oneultrasound transducer 20, the ultrasound transducers 20 can be connectedin parallel, in series or independently connected. Wires extending fromthe one or more ultrasound transducers 20 can be threaded up through oneor more lumens 38 in the extension body 64.

During the formation of the catheter and/or formation of the ultrasoundassemblies 10, one or more sensors can be included in any of the mediadescribed above. The sensor can be positioned within a volume before amedium is delivered into the volume. Alternatively, the sensor can bedelivered into a binding medium 42 precursor while the binding medium 42precursor is in a flowable state. Wires extending from the one or moresensors can be threaded up through one or more lumens 38 in theextension body 64. Suitable sensors for use with the catheter include,but are not limited to, a temperature sensor. When a catheter includesone or more temperature sensors, the temperature sensor is preferablypositioned adjacent to the external side 22 of an ultrasound transducer20. Specifically, the one or more temperature sensors are preferablypositioned in a volume between the external side 22 of the ultrasoundtransducer 20 and the external surface 53 of the catheter body 52.

The solidification of the binding medium 42 precursors can occurconcurrently or independently of one another. As discussed with respectto FIGS. 5A-5F, the binding medium 42 precursor and the second bindingmedium 42B precursor preferably solidify to different degrees ofhardness.

Binding medium 42 precursors for use with the catheters and ultrasoundassemblies 10 discussed above are preferably flowable to optimizedelivery into a desired volume. These precursors preferably solidify toa binding medium 42 having a reduced flowability. These precursors morepreferably solidify to a binding medium 42 having a reduced flowabilityand an increased degree of adhesiveness. This solidification can occurthrough mechanisms including, but not limited to, cooling, setting andcuring. Suitable binding media precursors and/or binding media include,but are not limited to, adhesives, epoxies, polymers, plastics, rubbers.Examples of suitable binding media with different degrees of hardnessare EPOTEK 310 having a hardness of about 22 Shore D and HYSOL 3561 and2939 having a hardness of about 85 Shore D. The binding media to be usedcan be selected for its particular hardness. Alternatively, bindingmedia, such as epoxies, cure to a different hardness based on thecomponent ratio in the binding media. The component ratio can beadjusted to achieve the desired hardness.

The binding media adjacent to the external side 22 of the ultrasoundtransducer 20 and/or adjacent to the ends of the ultrasound transducer20 preferably has an acoustic impedance of about 1-20 Megarayls, morepreferably about 1.3-10 Megarayls and most preferably about 4-8Megarayls. As described above, the low acoustic impedance mediumcontained within the chambers preferably has an acoustic impedance lessthan about 1.7 Megarayls, more preferably of about 0-0.7 Megarayls andmost preferably from 0-0.4 Megarayls. Further, the ratio of the acousticimpedances for the binding medium adjacent to the external side and/oradjacent ends the of the ultrasound transducer 20 measured relative tothe acoustic impedance of the low acoustic impedance medium containedwithin the chambers is preferably at least 1.5:1, more preferably atleast 2:1 and most preferably at least 4:1. Additionally the ratio ispreferably 1.5:1 to 10,000:1, more preferably about 1.5:1 to 100:1 andmost preferably 1.5:1 to 4:1.

FIG. 11 illustrates the proximal portion 72 of a catheter according tothe present invention. An electrical coupling 74 extends from theproximal portion 72 of the catheter. The electrical coupling 74 can becoupled with a catheter control system (not shown) for adjusting thefrequency and power of ultrasound energy delivered from the catheter.These adjustments can be made in response to signals from one or moresensors included with the catheter. For instance, these adjustments canbe made in response to signals form a temperature sensor in order tomaintain the temperature at a treatment site within a particular range.

The electrical coupling 74 includes an autotransformer 76 for adjustingthe characteristic impedance of the catheter to match the impedance ofan amplifier included in the catheter control system. For instance, ifthe amplifier has an input impedance of 50 ohms and the catheter has acharacteristic impedance of 40 ohms, the addition of the autotransformercan provide the catheter with a characteristic impedance of about 50ohms. The matched impedance serves to increase the efficiency of thecatheter system.

Because each catheter can have a different characteristic impedance, thewindings on the autotransformer can be adjusted to match the particularcatheter of interest. As a result, a method of assembling a catheter caninclude the step of providing an autotransformer which matches thecharacteristic impedance of the catheter to the characteristic impedanceof a component in a catheter control system.

The electrical coupling also includes catheter identificationelectronics 78. The catheter identification electronics 78 indicate tothe catheter control system what frequency the catheter should bedriven. For instance, the catheter identification electronics 78 can beone or more resistors. The catheter control system can include logic foridentifying the resistance. This resistance can be associated with acatheter of a particular frequency. The logic can identify theparticular frequency of the catheter and can then cause the catheter tobe driven at the indicated frequency. A computer chip is another exampleof suitable catheter identification electronics 78. The computer chipcan produce signals indicating the frequency of the catheter to thecatheter control system. In response, the catheter control system candrive the catheter at the appropriate frequency.

A catheter according to the present invention can be used by itself orcan be used in conjunction with a sheath 82 as illustrated in FIGS.12A-12D. Additional sheath and catheter embodiments are provided in U.S.patent application Ser. No. 09/107,078, filed Jun. 29, 1998 and entitledSheath for Use with an Ultrasound Element which is incorporated hereinin its entirety. FIG. 12A illustrates a sheath 82 configured to receivethe catheter. The sheath 82 includes a sheath proximal end 84 and asheath distal end 86. A catheter receiving lumen 88 extends through thesheath 82 and is sized to receive the catheter as illustrated in FIG.12B. The sheath distal end 86 preferably includes an energy deliveryportion which is constructed from a material which efficiently transmitsultrasound energy. Suitable materials for both the sheath 82 and theenergy delivery section 90 include, but are not limited to,polyethylene.

The catheter can be rotated or moved within the sheath 82 as illustratedby the arrow labeled A. The movement of the catheter within the sheath82 can be caused by manipulating the proximal portion of the catheterbody 52 while holding the sheath proximal end 84 stationary. Althoughnot illustrated, the sheath distal end 86 can include on or moretemperature sensors.

As illustrated in FIGS. 12C-12D, the sheath 82 can also optionallyinclude a drug delivery lumen 92. The drug delivery lumen 92 can includeone or more drug delivery ports 94 through which a drug can bedelivered. The drug delivery lumen 92 can be straight but is preferablycurved and more preferably spirals around the catheter receiving lumen88 as illustrated in FIGS. 12C and 12D. The drug delivery lumen 92preferably has a diameter/width of about 0.0005″-0.005″ and morepreferably about 0.001″-0.003″.

The drug delivery ports 94 are positioned close enough to achieve asubstantially even flow of drug solution around the circumference of thesheath 82. The proximity of adjacent drug delivery ports 94 can bechanged by changing the density of drug delivery ports 94 along the drugdelivery lumen 92 or by changing the number of windings of the drugdelivery lumen 92 around the energy delivery section 90. Suitabledisplacement between adjacent drug delivery ports 94 includes, but isnot limited to, from 0.1″ to 1.0″, preferable 0.2″ to 0.6″.

The size of the drug delivery ports 94 can be the same or change alongthe length of the drug delivery lumen 92. For instance, the size of thedrug delivery ports 94 distally positioned on the drug delivery sectioncan be larger than the size of the drug delivery ports 94 which areproximally positioned on the drug delivery section. The increase insizes of the drug delivery ports 94 can be designed to produce similarflowrates of drug solution through each drug delivery port 94. Thissimilar flowrate increases the uniformity of drug solution flowratealong the length of the sheath 82. When the drug delivery ports 94 havesimilar sizes along the length of the drug delivery lumen 92, a suitablesize for a drug delivery port includes, but is not limited to 0.0005″ to0.0050″. When the size of the drug delivery ports 94 changes along thelength of the drug delivery lumen 92, suitable sizes for proximallypositioned drug delivery ports 94 includes, but is not limited to from0.0001″ to 0.005″ and suitable sizes for distally positioned drugdelivery ports 94 includes, but is not limited to, 0.0005″ to 0.0020″.The increase in size between adjacent drug delivery ports 94 can besubstantially uniform between or along the drug delivery lumen 92. Thedimensional increase of the drug delivery ports 94 is dependent uponmaterial and diameter of the drug delivery lumen 92. The drug deliveryports 94 can be formed by burnt into the sheath 82 with a laser.

Uniformity of the drug solution flow along the length of the sheath 82can also be increased by increasing the density of the drug deliveryports 94 toward the distal end of the drug delivery lumen 92.

The drug delivery ports 94 can optionally be closed slits in the sheath82. The slits can have a straight or arcuate shape. When the dugdelivery lumen 92 contains drug solution, the slits remain closed untilthe pressure within the drug delivery lumen 92 exceeds a thresholdpressure. As the pressure within the drug delivery lumen 92 builds thepressure on each of the slits will be approximately uniform. Once, thethreshold pressure is reached, the uniform pressure will result in theslits opening almost simultaneously and cause a nearly uniform flow ofdrug solution out of all the slits. When the pressure within the drugdelivery lumen 92 falls below the threshold pressure, the slits closeand prevent delivery of additional drug solution. The stiffer thematerial used to construct the drug deliver lumen 38, the higher thethreshold pressure required to open the slit shaped drug delivery ports94. The slit shape can also prevent the drug delivery ports 94 fromopening when exposed to low pressures from outside the sheath 82. As aresult, slit shaped drug delivery ports 94 can maximize control of drugdelivery.

FIGS. 13A-13G illustrate a method for using the catheter with a sheath82. In FIG. 13A, a guidewire is directed through vessels toward atreatment site which includes a clot. The guidewire is directed throughthe clot. Suitable vessels include, but are not limited to,cardiovascular vessels, the pancreas, sinuses, esophagus, rectum,gastrointestinal vessels and urological vessels.

In FIG. 13B, the catheter receiving lumen 88 of the sheath 82 is slidover the guidewire and the sheath 82 is advanced along the guidewireusing traditional over-the-guidewire techniques. The sheath 82 isadvanced until the sheath distal end 86 is positioned at the clot. Radioopaque markers may be positioned at the sheath distal end 86 to aid inthe positioning of the sheath 82 within the treatment site.

In FIG. 13C, the guidewire is withdrawn from the utility lumen 38 bypulling the guidewire proximally while holding the sheath 82 stationary.In FIG. 13D, a drug solution source is coupled with the drug inlet port.The drug solution source can be a syringe with a Luer fitting which iscomplementary with the drug inlet port. Pressure can be applied to aplunger on the drug solution source to drive the drug solution throughthe drug delivery lumen 92. The drug solution is delivered from the drugdelivery lumen 92 through the drug delivery ports 94 as illustrated bythe arrows in FIG. 13E. Suitable drug solutions include, but are notlimited to, an aqueous solution containing Heparin, Uronkinase,Streptokinase, or tissue Plasminogen Activator (TPA).

In FIG. 13F, the catheter is inserted into the catheter receiving lumen88 until the ultrasound assembly 10 is positioned at the sheath distalend 86. To aid in placement of the catheter within the sheath 82,radiopaque markers may be positioned on the catheter adjacent to each ofthe ultrasound transducers 20. Alternatively, the ultrasound transducers20 themselves can be radiopaque. Once the catheter is properlypositioned, the ultrasound transducer 20 is activated to deliverultrasound energy through the sheath 82 to the treatment site. Suitableultrasound energy is delivered with a frequency from 5 KHz to 100 MHz,more preferably from 10 KHz to 25 MHz and most preferably from 20 KHz to5 MHz. While the ultrasound energy is being delivered, the ultrasoundtransducer 20 can be moved within the energy delivery section 90 asillustrated by the arrows labeled A. The movement of the ultrasoundtransducer 20 within the energy delivery section 90 can be caused bymanipulating the body proximal section while holding the sheath proximalend 84 stationary.

FIG. 14A illustrates an ultrasound catheter 110 which includes aplurality of ultrasound elements 112, temperature sensors 113 and drugdelivery ports 114 positioned along a selected section of the catheter110. The catheter 110 also includes a guidewire lumen 115 which canaccommodate a guidewire 116. At least one drug delivery port 114 iscorrelated with each ultrasound element 112.

In operation, the ultrasound elements 112 and drug delivery ports 114can be positioned adjacent a large lesion 118 in a vessel 120 asillustrated in FIG. 14B. Discrete ultrasound elements 112 are used incomparison to one continuous ultrasound element. Catheters introducedthrough circulatory vessels must be flexible in order to reach a desiredlocation where the lesion 118 is located. When a large lesion 118 ispresent, a single ultrasound element which is long enough to deliverultrasound energy the length of the lesion reduces the flexibility ofthe catheter 110. Therefore, multiple segmented ultrasound elements 112provide an increased flexibility over a long single element.

The average power required to activate an ultrasound element 112 isproportional to the activated area of the ultrasound element 112. Hence,a 2-cm long element requires approximately twice as much power as a 1-cmlong element of similar shape and diameter. As the power increases, thediameter of the electrical wires that bring electrical energy to theultrasound elements 112 must also increase. This requires an increase incatheter diameter that in turn reduces flexibility and restricts use ofthe catheter 110 in larger vessels.

These difficulties are solved by the present invention that creates adistribution of smaller ultrasound elements 112. The ultrasound elements112 are sized small enough so that they in combination with the catheter110 provide a flexible structure that can be moved down a tortuous veintree to the site of the lesion 118 or to any vessel in which there is alengthy lesion 118 to be treated. Additionally, the ultrasound elements112 are small enough that each individual ultrasound element 112, ifexcited individually, does not take an inordinate amount of powerthrough the wires which supply power to the catheter 110. The ultrasoundelements 112 are positioned to reduce dead space between the ultrasoundelements 112. This provides some overlap in the radiation patterns thatemit from each of the ultrasound elements 112 to maximize theenhancement effect. There is also a proximity between the ultrasoundelement 112 and the drug delivery ports 114 so that the drug emittedproximal or next to the catheter 110 is then affected by a nearby sourceof ultrasound energy. However, the drug delivery ports 114 do not needto be correlated with a particular ultrasound element 112 and there needbe no relationship between the number of drug delivery ports 114 and thenumber of ultrasound elements 112.

The ultrasound energy can be generated at an ultrasound energy sourcelocated external to the body and transmitted via wire to the ultrasoundelements. Ultrasound can also be internally generated from electricalpower delivered to the ultrasound elements from an electrical energysource. A suitable example of an ultrasound element for internalgeneration of ultrasound energy includes, but is not limited to, apiezoelectric ceramic oscillators. The ultrasound elements can be shapedas a cylinder, a hollow cylinder and a disk which are concentric withthe catheter. The ultrasound elements can also be an array of smallerultrasound elements or a thin plate positioned within the body of thecatheter. Similarly, a single ultrasound element can be composed ofseveral smaller ultrasound elements.

The individual ultrasound elements 112 can each be individually powered.When the catheter includes N ultrasound elements, the catheter body mustinclude 2N wires to individually power N ultrasound elements 112. Theindividual ultrasound elements 112 can also be electrically coupled inserial or in parallel as illustrated in FIGS. 15A and 15B. Thesearrangements permit maximum flexibility as they require only 2N wires.Each of the ultrasound elements receives power simultaneously whetherthe ultrasound elements are in series or in parallel. When theultrasound elements 112 are in series, less current is required toproduce the same power from each ultrasound element 112 than when theultrasound elements 112 are connected in parallel. The reduced currentallows smaller wires to be used to provide power to the ultrasoundelements 112 and accordingly increases the flexibility of the catheter110. When the ultrasound elements 112 are connected in parallel, anultrasound element 112 can break down and the remaining ultrasoundelements 112 will continue to operate.

As illustrated in FIG. 15C, a common wire 122 can provide power to eachof the ultrasound elements 112 while each ultrasound element 112 has itsown return wire 124. A particular ultrasound elements 112 can beindividually activated by closing a switch (not shown) to complete acircuit between the common wire 122 and the particular ultrasoundelement's return wire 124. Accordingly, a catheter with N ultrasoundelements requires only N+1 wires and still permits independent controlof the ultrasound elements 112. This reduced number of wires increasesthe flexibility of the catheter 110. To improve the flexibility of thecatheter, the individual return wires can have diameters which aresmaller than the common wire diameter. For instance, in an embodimentwhere N ultrasound elements will be powered simultaneously, the diameterof the individual wires can be the square root of N times smaller thanthe diameter of the common wire.

As illustrated in FIG. 14A, a temperature sensor 113 is positionedadjacent each ultrasound element 112. Suitable temperature sensors 113include, but are not limited to, thermistors, thermocouples andresistance temperature detectors, RTDs, and fiber optic temperaturesensors which use thermalchromic liquid crystals. Suitable temperaturesensor 113 geometries include, but are not limited to, a point, patch,stripe and a band around the catheter 10 as illustrated. The temperaturesensors 113 can be positioned on the catheter 110, on the ultrasoundelement and adjacent the ultrasound elements 112 as illustrated.

The temperature sensors 113 can be electrically connected as illustratedin FIG. 15C. Each temperature sensor 113 can be coupled with a commonwire 122 and then include its own return wire 124. Accordingly, N+1wires can be used to independently sense the temperature at thetemperature sensors 113 of a catheter 110 having N temperature sensors113. A suitable common wire 122 can be constructed from Constantine andsuitable return 124 wires can be constructed from copper. Thetemperature at a particular temperature sensor 113 can be determined byclosing a switch (not shown) to complete a circuit between thethermocouple's return wire 124 and the common wire 122. When thetemperature sensors 113 are thermocouples, the temperature can becalculated form the voltage in the circuit. To improve the flexibilityof the catheter, the individual return wires can have diameters whichare smaller than the common wire diameter.

Each temperature sensor 113 can also be independently wired. A catheter110 including N temperature sensors 113 which are independently wiredwill require 2N wires to pass the length of the catheter.

The catheter flexibility can also be improved by using fiber optic basedtemperature sensors. The flexibility can be improved because only Nfiber optics need to be included in the catheter to sense thetemperature at N temperature sensors.

The temperature sensors 113 do not need to be correlated with theultrasound elements 112. For instance, the catheter 110 can include atemperature sensor 113 which is positioned to provide a signalindicating the temperature of the portion of the lumen being treated.For instance, the temperature sensor 113 can be positioned between thecentral two ultrasound elements. The ultrasound output from theultrasound elements 112 can be manually or automatically adjusted inresponse to the signal from the temperature sensor 113.

The drug delivery ports 114 can be coupled with a common lumen 125 asillustrated in FIG. 16A. The drug delivery ports 114 can be positionedon one side of the catheter 110 or distributed about the surface of thecatheter 110 to provide a more even delivery of the drug. A drug can bedelivered through the common lumen 125 to the various drug deliveryports 114 next to each of the ultrasound elements 112 so that all of thedrug delivery ports 114 deliver drug at the same time. As illustrated inFIG. 16B, one or more drug delivery ports 126 can be coupled with afirst lumen 127 and one or more second drug delivery ports 128 can becoupled with a second lumen 129. Accordingly, different drugs can bedelivered adjacent different ultrasound elements 112. Further, differentamounts of the same drug can be delivered adjacent particular ultrasoundelements 112. As a result, the amount of drug delivery can be adjustedto match the amount of therapeutic treatment required by a particularsection of the lesion 118. Use of the ultrasound elements 112 and aplurality of drug delivery ports 114 can provide controllability andselectability of lesion modification/destruction.

The catheter 110 can be used in various body structures and body lumensincluding, but not limited to, the pancreas, sinuses, esophagus, rectum,gastrointestinal vessels and urological vessels. The catheter 110 isselected from a variety of different sizes, diameter and length,depending on the type and location of the lesion 118. An active lengthof catheter 110 is defined by the number and spacing of the ultrasoundelements 112 and drug delivery ports 114 at the distal end. The numberof ultrasound elements 112 depends on the length of the vessel beingtreated. Suitable numbers of ultrasound elements include, but are notlimited to 2-10, 2-8 and 4-6. Each of the ultrasound elements 112 can befrom one millimeter in length to up to a half centimeter in length.Other dimensions can also be used. The spacing between ultrasoundelements 112 can be approximately equal to the length of each ultrasoundelement 112. If one ultrasound element 112 has a length L, a secondultrasound element 112 can be spaced up to three L lengths away from thefirst ultrasound element 112. Suitable L include, bur are not limited to0.2-2 cm, 0.2-1.2 cm and 0.3-0.7 cm.

The catheter 110 can be constructed to overcome the reduced flexibilitywhich results from the multiple ultrasound elements 112. As illustratedin FIG. 17A, the catheter 110 can include ribs 130 between theultrasound elements 112. The ribs 130 increase the bendability of thecatheter at the ribbed locations while providing kink resistance. Theadded flexibility can be necessary to work the catheter 110 throughtortuous vessels. As illustrated in FIG. 17B additional flexibility canbe obtained by manufacturing at least the portion of the catheter 110between the ultrasound elements 112 from a mesh 132 or braided material.As illustrated in FIG. 17C, the outer surface of the catheter 110 andthe lumens within the catheter 110 are smooth 134. The smooth surfaces134 aid in passing the catheter 110 through the body lumen and inpassing fluids through the lumen. Any wires 135 present in the catheter110 can pass through the mesh portion of the catheter 110 for additionalflexibility. Suitable materials for the catheter include, but are notlimited to polyolefins and polyimides and other low acoustic impedancematerials. Low accoustic impedance materials are materials which readilytransmit ultrasound energy with minimal absorption of the energy.Suitable materials for the mesh or braid include, but are not limited toKevlar, stainless steel, polyetheretherketone or PEEK. Cotton braidedwith polymer can also serve to provide flexibility and kink resistance.

The ultrasound elements 112 can be positioned internally or externallyto catheter 110, and can have any number of different geometric designs.Suitable, geometric designs include, but are not limited to a band whichlies flush with the circumference of the catheter. Additionally,ultrasound elements 112 can be designed provide any desireddirectionality of ultrasound.

The catheter 110 can be coupled with an open or closed loop feedbacksystem. Referring now to FIG. 18 an open or closed loop feedback systemcouples temperature sensor 113 to an energy source 140. The temperatureof the tissue, or of each ultrasound element 112 is monitored, and theoutput power of energy source 140 adjusted accordingly. The physiciancan, if desired, override the closed or open loop system. A processingunit 142 can be included and incorporated in the closed or open loopsystem to switch power on and off, as well as modulate the power. Theprocessing unit 142 includes logic for monitoring the temperature ateach temperature sensor 113, adjusting the power delivered to eachultrasound element 112, re-monitoring the temperature at eachtemperature sensor 113 and re-adjusting the power delivered to theultrasound elements 112 in response to the re-monitored temperature.

With the use of the temperature sensors 113 and the feedback controlsystem, the tissue adjacent to the ultrasound elements 112 can bemaintained at a desired temperature for a selected period of time. Eachultrasound element 112 is connected to resources which generate anindependent output. The output maintains a selected energy at eachultrasound element 112 for a selected length of time.

Power delivered to the ultrasound elements 112 is measured by the powercalculation device 144. The power can then be displayed at userinterface and display 146. Signals representative of power and impedancevalues are received by the processing unit 142.

A control signal is generated by the processing unit 142 that isproportional to the difference between an actual measured value, and adesired value. The control signal is used by power circuits 147 toadjust the power output in an appropriate amount in order to maintainthe temperature at each ultrasound element 112 within a desired range.

The temperatures detected at the temperature sensors 113 providefeedback for maintaining the desired temperature range. The temperatureat each temperature sensor 112 can be used as safety devices tointerrupt the delivery of energy when maximum pre-set temperatures areexceeded. The temperature at each ultrasound sensor 112 is measured attemperature measurement device 148, and can be displayed at userinterface and display 146. A temperature control signal is generated bythe processing unit 142 that is proportional to the difference betweenan actual measured temperature and a desired temperature. Thetemperature control signal is used to determine the desired power. Forinstance, when the control signal exceeds a pre-determined level, thedesired power supplied to a particular ultrasound element can be reducedor turned off. Similarly, when the control signal falls below apre-determined level, the desired power supplied to a particularultrasound element 112 can be increased or turned on.

The processing unit 142 can be a digital or analog controller, or acomputer with software. When the processing unit 142 is a computer itcan include a CPU coupled through a system bus. On this system can be akeyboard, a disk drive, or other non-volatile memory systems, a display,and other peripherals, as are known in the art. Also coupled to the busis a program memory and a data memory.

User interface and display 146 includes operator controls and a display.

The output of the temperature sensors 113 is used by the processing unit142 to maintain a selected temperature range at each temperature sensor113. A profile of the power delivered to each ultrasound element 112 canbe incorporated in the processing unit 142 and a preset amount of energyto be delivered may also be profiled.

Circuitry, software and feedback to the processing unit 142 result inprocess control, and the maintenance of the selected power setting thatis independent of changes in voltage or current, and used to change, (i)the selected power setting, (ii) the duty cycle (on-off time), (iii)bipolar or monopolar energy delivery and (iv) fluid delivery, includingflow rate and pressure. These process variables are controlled andvaried, while maintaining the desired delivery of power independent ofchanges in voltage or current, based on temperatures monitored at thetemperature sensor 113.

The catheter 110 is guided along the artery or vein to the lesion siteby fluoroscopy. Radio opaque markers may be used with the catheter 110next to each of the ultrasound elements 112, or in the case of certainpiezoelectric elements 112, the ultrasound elements 112 themselves areradio opaque and readily identified and also readily identify the siteof the adjacent drug port 114. The catheter 110 is advanced through thevessel with the assistance of a guidewire. The catheter can be advanceduntil each of the ultrasound elements are adjacent the lesion or untilonly a portion of the ultrasound elements are adjacent the lesion. Thedrug is hydraulically delivered through the lumen to the drug deliveryports 114. The ultrasound elements 112 are then all turned on together,sequenced or multiplexed according to the preferred treatment by thephysician. The feedback control system is then engaged to control thetemperature of within the vessel. The catheter 110 remains in place forthe treatment period and the drug can be continually infused with theultrasound elements 112 on, off, partially on, or partially off. After asection of the vessel is treated, the catheter can be advanced to treatadditional untreated portions of the vessel. The ultrasound elementswhich are used to treat the additional untreated portion can bedifferent from the ultrasound elements used during the initialtreatment(s). When the desired clinical result is obtain, as verified byfluoroscopy, the catheter 110 is removed.

Segmentation of ultrasound elements 112 greatly reduces the requiredamount of a lumen of the catheter 110 that is used for segment wiring,increases the flexibility of the catheter 110, and permits radiation ofa long lesion 118. When a single continuous length ultrasound element isused the power requirements necessitate the use of thick wires. This iseliminated with the use of ultrasound elements 112 in segment form.Replacement of one large wire by multiple wires of equivalentcross-sectional area or a cumulated cross-section area is more flexibleand also avoids having to excite entirely a long ultrasound element,smaller ultrasound elements 112 that are segmented are used. Therefore,a fraction of the power at any one time is needed, depending on thenumber of ultrasound elements 112 activated.

While the present invention is disclosed by reference to the preferredembodiments and examples detailed above, it is to be understood thatthese examples are intended in an illustrative rather than limitingsense, as it is contemplated that modifications and combinations willreadily occur to those skilled in the art, which modifications andcombinations will be within the spirit of the invention and the scope ofthe appended claims.

1. A catheter for providing a therapeutic effect to a vessel of a body,comprising: an elongated body having a lumen coupled with a drugdelivery port through which a drug within the lumen can exit the lumen;and a plurality of ultrasound elements where each of the plurality ofultrasound elements is separated from an adjacent ultrasound element andat least two of the ultrasound elements are positioned on opposite sidesof the drug delivery port and close enough to the drug delivery portthat a drug delivered from the drug delivery port is exposed toultrasound energy delivered from at least one of the ultrasoundelements, the delivered drug and ultrasound energy providing thetherapeutic effect to the vessel.
 2. The catheter of claim 1, where eachof the plurality of ultrasound elements is separated from an adjacentultrasound element by approximately 1 cm.
 3. The catheter of claim 1,further comprising: a temperature sensor.
 4. The catheter of claim 3,wherein the temperature sensor is positioned to detect the temperatureof a surface of an ultrasound element.
 5. The catheter of claim 3,further comprising: a feedback control system configured to adjust alevel of ultrasound delivered from the plurality of ultrasound elementsin response to a signal from the temperature sensor.
 6. The catheter ofclaim 1, further comprising: a plurality of temperature sensors.
 7. Thecatheter of claim 1, further comprising: a feedback control system foradjusting a level of ultrasound delivered from a particular ultrasoundelements in response to a signal from a particular temperature sensor.8. The apparatus of claim 1, further comprising: at least one seconddrug delivery port coupled with the lumen.
 9. The catheter of claim 8,wherein the at least one second drug delivery port is positioned betweenadjacent ultrasound elements.
 10. The catheter of claim 8, furthercomprising: a second lumen extending through the catheter; and at leastone second drug delivery port coupled with the second lumen to deliver adrug from the second lumen to the vessel.
 11. The catheter of claim 1,further comprising: a flexibility providing structure positioned betweena two of the plurality of ultrasound elements.
 12. The catheter of claim11, wherein the flexibility providing structure is at least one rib. 13.The catheter of claim 11, wherein the flexibility providing structure isa braided material.
 14. The catheter of claim 11, wherein theflexibility providing structure is a mesh material.
 15. The catheter ofclaim 1, wherein a first portion of each ultrasound element is coupledwith a common wire and a second portion of each ultrasound element iscoupled with a different wire.
 16. The catheter of claim 1, wherein eachof the plurality of ultrasound elements are connected in series.
 17. Thecatheter of claim 1, wherein each of the plurality of ultrasoundelements are connected in parallel.
 18. The catheter of claim 1, whereineach of the plurality of temperature sensors are connected through acommon wire.
 19. A catheter for providing a therapeutic effect to avessel of a body, comprising: an elongated body having a lumen coupledwith a drug delivery port through which a drug within the lumen can exitthe lumen; a plurality of ultrasound elements where each of theplurality of ultrasound elements is separated from an adjacentultrasound element and at least two of the ultrasound elements arepositioned on opposite sides of the drug delivery port; and close enoughto the drug delivery port that a drug delivered from the drug deliveryport is exposed to ultrasound energy delivered from at least one of theultrasound elements, the delivered drug and ultrasound energy providingthe therapeutic effect to the vessel; and a flexibility providingstructure positioned between two ultrasound elements among the pluralityof ultrasound elements.
 20. The catheter of claim 19, where each of theplurality of ultrasound elements is separated from an adjacentultrasound element by approximately 1 cm.
 21. The catheter of claim 19,wherein the flexibility providing structure is at least one rib.
 22. Thecatheter of claim 19, wherein the flexibility providing structure is abraided material.
 23. The catheter of claim 19, wherein the flexibilityproviding structure is a mesh material.
 24. A catheter for providing atherapeutic effect to a vessel of a body, comprising: an elongated bodyhaving a lumen coupled with a plurality of drug delivery ports throughwhich a drug within the lumen can exit the lumen; a plurality ofultrasound elements where each of the plurality of ultrasound elementsis separated from an adjacent ultrasound element and is close enough toone of plurality of drug delivery ports that a drug delivered from thedrug delivery port is exposed to ultrasound energy delivered from theultrasound element, the delivered drug and ultrasound energy providingthe therapeutic effect to the vessel.
 25. The catheter of claim 24,where each of the plurality of ultrasound elements is separated from anadjacent ultrasound element by approximately 1 cm.